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Antimicrobial Agents and Chemotherapy Oct 2022This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing...
This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.
Topics: Humans; Aztreonam; Retrospective Studies; beta-Lactamases; Microbial Sensitivity Tests; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Gram-Negative Bacteria; Drug Combinations
PubMed: 36102635
DOI: 10.1128/aac.00751-22 -
The Cochrane Database of Systematic... May 2021Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality....
BACKGROUND
Neonatal sepsis is a major cause of morbidity and mortality. It is the third leading cause of neonatal mortality globally constituting 13% of overall neonatal mortality. Despite the high burden of neonatal sepsis, high-quality evidence in diagnosis and treatment is scarce. Due to the diagnostic challenges of sepsis and the relative immunosuppression of the newborn, many neonates receive antibiotics for suspected sepsis. Antibiotics have become the most used therapeutics in neonatal intensive care units, and observational studies in high-income countries suggest that 83% to 94% of newborns treated with antibiotics for suspected sepsis have negative blood cultures. The last Cochrane Review was updated in 2005. There is a need for an updated systematic review assessing the effects of different antibiotic regimens for late-onset neonatal sepsis.
OBJECTIVES
To assess the beneficial and harmful effects of different antibiotic regimens for late-onset neonatal sepsis.
SEARCH METHODS
We searched the following electronic databases: CENTRAL (2021, Issue 3); Ovid MEDLINE; Embase Ovid; CINAHL; LILACS; Science Citation Index EXPANDED and Conference Proceedings Citation Index - Science on 12 March 2021. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.
SELECTION CRITERIA
We included RCTs comparing different antibiotic regimens for late-onset neonatal sepsis. We included participants older than 72 hours of life at randomisation, suspected or diagnosed with neonatal sepsis, meningitis, osteomyelitis, endocarditis, or necrotising enterocolitis. We excluded trials that assessed treatment of fungal infections.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We used the GRADE approach to assess the certainty of evidence. Our primary outcome was all-cause mortality, and our secondary outcomes were: serious adverse events, respiratory support, circulatory support, nephrotoxicity, neurological developmental impairment, necrotising enterocolitis, and ototoxicity. Our primary time point of interest was at maximum follow-up.
MAIN RESULTS
We included five RCTs (580 participants). All trials were at high risk of bias, and had very low-certainty evidence. The five included trials assessed five different comparisons of antibiotics. We did not conduct a meta-analysis due to lack of relevant data. Of the five included trials one trial compared cefazolin plus amikacin with vancomycin plus amikacin; one trial compared ticarcillin plus clavulanic acid with flucloxacillin plus gentamicin; one trial compared cloxacillin plus amikacin with cefotaxime plus gentamicin; one trial compared meropenem with standard care (ampicillin plus gentamicin or cefotaxime plus gentamicin); and one trial compared vancomycin plus gentamicin with vancomycin plus aztreonam. None of the five comparisons found any evidence of a difference when assessing all-cause mortality, serious adverse events, circulatory support, nephrotoxicity, neurological developmental impairment, or necrotising enterocolitis; however, none of the trials were near an information size that could contribute significantly to the evidence of the comparative benefits and risks of any particular antibiotic regimen. None of the trials assessed respiratory support or ototoxicity. The benefits and harms of different antibiotic regimens remain unclear due to the lack of well-powered trials and the high risk of systematic errors.
AUTHORS' CONCLUSIONS
Current evidence is insufficient to support any antibiotic regimen being superior to another. RCTs assessing different antibiotic regimens in late-onset neonatal sepsis with low risks of bias are warranted.
Topics: Amikacin; Ampicillin; Anti-Bacterial Agents; Aztreonam; Bias; Cefazolin; Clavulanic Acid; Drug Therapy, Combination; Floxacillin; Gentamicins; Humans; Infant, Newborn; Neonatal Sepsis; Randomized Controlled Trials as Topic; Ticarcillin; Vancomycin
PubMed: 33998665
DOI: 10.1002/14651858.CD013836.pub2 -
Expert Review of Anti-infective Therapy Apr 2024Metallo-beta-lactamases (MBLs) are responsible for resistance to almost all beta-lactam antibiotics. Found predominantly in Gram-negative bacteria, they severely limit... (Review)
Review
INTRODUCTION
Metallo-beta-lactamases (MBLs) are responsible for resistance to almost all beta-lactam antibiotics. Found predominantly in Gram-negative bacteria, they severely limit treatment options. Understanding the epidemiology, risk factors, treatment, and prevention of infections caused by MBL-producing organisms is essential to reduce their burden.
AREAS COVERED
The origins and structure of MBLs are discussed. We describe the mechanisms of action that differentiate MBLs from other beta-lactamases. We discuss the global epidemiology of MBL-producing organisms and their impact on patients' outcomes. By exposing the mechanisms of transmission of MBLs among bacterial populations, we emphasize the importance of infection prevention and control.
EXPERT OPINION
MBLs are spreading globally and challenging the majority of available antibacterial agents. Genotypic tests play an important role in the identification of MBL production. Phenotypic tests are less specific but may be used in low-resource settings, where MBLs are more predominant. Infection prevention and control are critical to reduce the spread of organisms producing MBL in healthcare systems. New combinations such as avibactam-aztreonam and new agents such as cefiderocol have shown promising results for the treatment of infections caused by MBL-producing organisms. New antibiotic and non-antibiotic agents are being developed and may improve the management of infections caused by MBL-producing organisms.
Topics: Humans; beta-Lactamases; Anti-Bacterial Agents; Aztreonam; Gram-Negative Bacteria; Bacteria; Microbial Sensitivity Tests; beta-Lactamase Inhibitors
PubMed: 38275276
DOI: 10.1080/14787210.2024.2311213 -
JAMA Jul 2023
Topics: Humans; Anti-Bacterial Agents; beta-Lactams; Critical Illness; Infusions, Intravenous; Monobactams; Sepsis; Treatment Outcome; Time Factors
PubMed: 37326478
DOI: 10.1001/jama.2023.6483 -
Revista Alergia Mexico (Tecamachalco,... 2022Betalactams are the most widely used antimicrobials for their safety and efficacy. These include the penicillins, cephalosporins, carbapenems, and monobactams....
Betalactams are the most widely used antimicrobials for their safety and efficacy. These include the penicillins, cephalosporins, carbapenems, and monobactams. Penicillin allergy ranks first in relation to drug allergy. 10 to 20 % of the population is labeled as allergic to it, often wrongly. Cross reaction is reported in 2 to 5 % between penicillins and cephalosporin. There is no cross reaction between penicillins and aztreonam, but there is with ceftazidime. All the mechanisms of the Gell and Coombs classification are included in the pathophysiology of hypersensitivity reactions to penicillin. Stratification according to risk allows us to take the most objective behavior to label the patient as allergic to. In the natural history of penicillin allergy, 80-90 % of patients lose this sensitivity by 10 years. If necessary, the patient can undergo a desensitization protocol. The immuno-allergist is a key piece in the selection of the patient, the elaboration of the challenge and desensitization protocols, in a controlled environment.
Topics: Anti-Bacterial Agents; Carbapenems; Cephalosporins; Cross Reactions; Drug Hypersensitivity; Humans; Penicillins; Skin Tests
PubMed: 34998313
DOI: 10.29262/ram.v69iSup1.1038 -
The Cochrane Database of Systematic... Nov 2022Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently... (Review)
Review
BACKGROUND
Typhoid and paratyphoid (enteric fever) are febrile bacterial illnesses common in many low- and middle-income countries. The World Health Organization (WHO) currently recommends treatment with azithromycin, ciprofloxacin, or ceftriaxone due to widespread resistance to older, first-line antimicrobials. Resistance patterns vary in different locations and are changing over time. Fluoroquinolone resistance in South Asia often precludes the use of ciprofloxacin. Extensively drug-resistant strains of enteric fever have emerged in Pakistan. In some areas of the world, susceptibility to old first-line antimicrobials, such as chloramphenicol, has re-appeared. A Cochrane Review of the use of fluoroquinolones and azithromycin in the treatment of enteric fever has previously been undertaken, but the use of cephalosporins has not been systematically investigated and the optimal choice of drug and duration of treatment are uncertain.
OBJECTIVES
To evaluate the effectiveness of cephalosporins for treating enteric fever in children and adults compared to other antimicrobials.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the WHO ICTRP and ClinicalTrials.gov up to 24 November 2021. We also searched reference lists of included trials, contacted researchers working in the field, and contacted relevant organizations.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in adults and children with enteric fever that compared a cephalosporin to another antimicrobial, a different cephalosporin, or a different treatment duration of the intervention cephalosporin. Enteric fever was diagnosed on the basis of blood culture, bone marrow culture, or molecular tests.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were clinical failure, microbiological failure and relapse. Our secondary outcomes were time to defervescence, duration of hospital admission, convalescent faecal carriage, and adverse effects. We used the GRADE approach to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 27 RCTs with 2231 total participants published between 1986 and 2016 across Africa, Asia, Europe, the Middle East and the Caribbean, with comparisons between cephalosporins and other antimicrobials used for the treatment of enteric fever in children and adults. The main comparisons are between antimicrobials in most common clinical use, namely cephalosporins compared to a fluoroquinolone and cephalosporins compared to azithromycin. Cephalosporin (cefixime) versus fluoroquinolones Clinical failure, microbiological failure and relapse may be increased in patients treated with cefixime compared to fluoroquinolones in three small trials published over 14 years ago: clinical failure (risk ratio (RR) 13.39, 95% confidence interval (CI) 3.24 to 55.39; 2 trials, 240 participants; low-certainty evidence); microbiological failure (RR 4.07, 95% CI 0.46 to 36.41; 2 trials, 240 participants; low-certainty evidence); relapse (RR 4.45, 95% CI 1.11 to 17.84; 2 trials, 220 participants; low-certainty evidence). Time to defervescence in participants treated with cefixime may be longer compared to participants treated with fluoroquinolones (mean difference (MD) 1.74 days, 95% CI 0.50 to 2.98, 3 trials, 425 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus azithromycin Ceftriaxone may result in a decrease in clinical failure compared to azithromycin, and it is unclear whether ceftriaxone has an effect on microbiological failure compared to azithromycin in two small trials published over 18 years ago and in one more recent trial, all conducted in participants under 18 years of age: clinical failure (RR 0.42, 95% CI 0.11 to 1.57; 3 trials, 196 participants; low-certainty evidence); microbiological failure (RR 1.95, 95% CI 0.36 to 10.64, 3 trials, 196 participants; very low-certainty evidence). It is unclear whether ceftriaxone increases or decreases relapse compared to azithromycin (RR 10.05, 95% CI 1.93 to 52.38; 3 trials, 185 participants; very low-certainty evidence). Time to defervescence in participants treated with ceftriaxone may be shorter compared to participants treated with azithromycin (mean difference of -0.52 days, 95% CI -0.91 to -0.12; 3 trials, 196 participants; low-certainty evidence). Cephalosporin (ceftriaxone) versus fluoroquinolones It is unclear whether ceftriaxone has an effect on clinical failure, microbiological failure, relapse, and time to defervescence compared to fluoroquinolones in three trials published over 28 years ago and two more recent trials: clinical failure (RR 3.77, 95% CI 0.72 to 19.81; 4 trials, 359 participants; very low-certainty evidence); microbiological failure (RR 1.65, 95% CI 0.40 to 6.83; 3 trials, 316 participants; very low-certainty evidence); relapse (RR 0.95, 95% CI 0.31 to 2.92; 3 trials, 297 participants; very low-certainty evidence) and time to defervescence (MD 2.73 days, 95% CI -0.37 to 5.84; 3 trials, 285 participants; very low-certainty evidence). It is unclear whether ceftriaxone decreases convalescent faecal carriage compared to the fluoroquinolone gatifloxacin (RR 0.18, 95% CI 0.01 to 3.72; 1 trial, 73 participants; very low-certainty evidence) and length of hospital stay may be longer in participants treated with ceftriaxone compared to participants treated with the fluoroquinolone ofloxacin (mean of 12 days (range 7 to 23 days) in the ceftriaxone group compared to a mean of 9 days (range 6 to 13 days) in the ofloxacin group; 1 trial, 47 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on very low- to low-certainty evidence, ceftriaxone is an effective treatment for adults and children with enteric fever, with few adverse effects. Trials suggest that there may be no difference in the performance of ceftriaxone compared with azithromycin, fluoroquinolones, or chloramphenicol. Cefixime can also be used for treatment of enteric fever but may not perform as well as fluoroquinolones. We are unable to draw firm general conclusions on comparative contemporary effectiveness given that most trials were small and conducted over 20 years previously. Clinicians need to take into account current, local resistance patterns in addition to route of administration when choosing an antimicrobial.
Topics: Child; Adult; Humans; Adolescent; Paratyphoid Fever; Typhoid Fever; Cephalosporins; Azithromycin; Ceftriaxone; Cefixime; Fluoroquinolones; Anti-Bacterial Agents; Chloramphenicol; Anti-Infective Agents; Monobactams; Ciprofloxacin; Ofloxacin; Recurrence; Pakistan
PubMed: 36420914
DOI: 10.1002/14651858.CD010452.pub2 -
Antimicrobial Agents and Chemotherapy Aug 2019Multidrug-resistant (MDR) Gram-negative organisms are a major health concern due to lack of effective therapy. Emergence of resistance to newer agents like...
Evaluation of the Synergy of Ceftazidime-Avibactam in Combination with Meropenem, Amikacin, Aztreonam, Colistin, or Fosfomycin against Well-Characterized Multidrug-Resistant Klebsiella pneumoniae and Pseudomonas aeruginosa.
Multidrug-resistant (MDR) Gram-negative organisms are a major health concern due to lack of effective therapy. Emergence of resistance to newer agents like ceftazidime-avibactam (CZA) further magnifies the problem. In this context, combination therapy of CZA with other antimicrobials may have potential in treating these pathogens. Unfortunately, there are limited data regarding these combinations. Therefore, the objective of this study was to evaluate CZA in combination with amikacin (AMK), aztreonam (AZT), colistin (COL), fosfomycin (FOS), and meropenem (MEM) against 21 carbapenem-resistant and 21 MDR strains. The potential for synergy was evaluated via MIC combination evaluation and time-kill assays. All strains were further characterized by whole-genome sequencing, quantitative real-time PCR, and SDS-PAGE analysis to determine potential mechanisms of resistance. Compared to CZA alone, we observed a 4-fold decrease in CZA MICs for a majority of strains and at least a 2-fold decrease for most isolates in the majority of combinations tested. In both and strains, CZA in combination with AMK or AZT was synergistic (≥2.15-log CFU/ml decrease). CZA-MEM was effective against and CZA-FOS was effective against Time-kill analysis also revealed that the synergy of CZA with MEM or AZT may be due to the previously reported restoration of MEM or AZT activity against these organisms. Our findings show that CZA in combination with these antibiotics has potential for therapeutic options in difficult to treat pathogens. Further evaluation of these combinations is warranted.
Topics: Amikacin; Azabicyclo Compounds; Aztreonam; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Drug Synergism; Fosfomycin; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 31182535
DOI: 10.1128/AAC.00779-19 -
Allergy Mar 2024In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has...
In drug hypersensitivity, drug provocation testing (DPT), also called drug challenge, is the gold standard for investigation. In recent years, risk stratification has become an important tool for adjusting the diagnostic strategy to the perceived risk, whilst still maintaining a high level of safety for the patient. Skin tests are recommended before DPT but may be omitted in low-risk patients. The task force suggests a strict definition of such low-risk patients in children and adults. Based on experience and evidence from studies of allergy to beta-lactam antibiotics, an algorithm on how to adjust DPT to the risk, and when to omit skin tests before DPT, is presented. For other antibiotics, non-steroidal anti-inflammatory drugs and other drugs, skin tests are poorly validated and DPT is frequently necessary. We recommend performing DPT with chemotherapeutics and biologicals to avoid unnecessary desensitization procedures and DPT with skin tests negative contrast media. We suggest DPT with anesthetics only in highly specialized centers. Specifics of DPT to proton pump inhibitors, anticonvulsants and corticosteroids are discussed. This position paper provides general recommendations and guidance on optimizing use of DPT, whilst balancing benefits with patient safety and optimizing the use of the limited available resources.
Topics: Child; Adult; Humans; Drug Hypersensitivity; Anti-Inflammatory Agents, Non-Steroidal; Contrast Media; Monobactams; beta Lactam Antibiotics; Skin Tests; Anti-Bacterial Agents
PubMed: 38155501
DOI: 10.1111/all.15996 -
Pharmacotherapy Aug 2023Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability.... (Review)
Review
International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases,...
Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).
Topics: Adult; Humans; Child; Pharmacists; Cystic Fibrosis; Anti-Infective Agents; Monobactams; Communicable Diseases; Anti-Bacterial Agents; Pharmacy
PubMed: 37615244
DOI: 10.1002/phar.2844